Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation
Authors: Catherine Boschert, Emma Broadfield, Timothy Chimunda, Jason Fletcher, Cameron Knott, Sanjay Porwal, Julie Smith, Deepak Bhonagiri, Monique Leijten, Sandhya Narayan, David Sanchez, Peta Saunders, Carli Sherriff, Jonathan Barrett, Gabrielle Hanlon, Sarah Jelly-Butterworth, Julie O'Donnell, Judith Watson, Shailesh Bihari, Julia Brown, Sharon Comerford, Russell Laver, JoAnne McIntyre, Tapaswi Shrestha, Jin Xia, Samantha Bates, Gerard Fennessy, Craig French, Sathyajith Kootayi, Fiona Marshall, Rebecca McEldrew, Forbes McGain, Rebecca Morgan, John Mulder, Anna Tippett, Miriam Towns, Ellie Barker, Shelley Donovan, Katrina Ellis, Atul Gaur, Hannah Gibbons, Rebecca Gregory, Eloise Hair, Mary Keehan, Jess Naumoff, Elisha Turner, Gail Brinkerhoff, Dustin Bush, Federica Cazzola, Ken Havill, Paul Healey, Amber Poulter, Krishna Sunkara, Anders Aneman, Rachel Choit, Kelsey Dobell-Brown, Kairui Guo, Jillian Lee, Lien Lombardo, Zachariah Manalil, Jennene Miller, Jordan Rogers, Antony Stewart, Jana Yanga, Rebecca Gresham, Julie Lowrey, Kristy Masters, Christina Whitehead, Beverly Zaratan, Matthew Grigg, Meg Harward, Cassie Jones, Josephine Mackay, Jason Meyer, Emma Saylor, Ellen Venz, James Walsham, Krista Wetzig, Nerissa Brown, Marianne Chapman, Kathleen Glasby, Samuel Gluck, Tejaswini Murthy, Stephanie O'Connor, Eamon Raith, Justine Rivett, Joannies Yap, Angela Ashelford, Frances Bass, Emily Fitzgerald, Oliver Flower, Bernard Hudson, Pierre Janin, Elizabeth Limbrey, Sharon Mar, Anne O'Connor, Melissa Owen, Naomi Pallas, Julia Pilowsky, Veronica Roach, Elizabeth Ruse, Wade Stedman, Miyuki Tokumitsu, Elizabeth Yarad, Deborah Inskip, Theresa Jacques, Adeline Kintono, Catherine Milner, Rebecca Sidoli, Catherine Kurenda, Sandra Peake, Patricia Williams, Jeremy Cohen, Amanda Davie, Amy Owens, Roslyn Purcell, Balasubramanian Venkatesh, Cartan Costello, Alan Davey-Quinn, Michael Davies, Ahmed Elgendy, Wenli Geng, Veerendra Jagarlamudi, Matthew Mac Partlin, Mahadev Patil, Adam Purdon, Martin Sterba, Andrea Marshall, Anthony Delaney, Marwa Abdel-All, Hayley Clark, Natalie Espinosa, Benjamin Finfer, Miranda Hardie, Dijlah Moungatonga, Conrad Nangla, Fiona Osbourne, Tina Schneider, Prakriti Shrestha, Elizabeth Wilson, Isabella Schoeler, Manuela Armenis, Dominic Byrne, Amrutha Nagarajaiah, Prakesh Velappan, Parisa Glass, Kate Myburgh, Philippa Smith, Martina Bachmaier, Daryll Knowles, Michael Tattersall, John A. Myburgh, Ian M. Seppelt, Fiona Goodman, Laurent Billot, Maryam Correa, Joshua S. Davis, Anthony C. Gordon, Naomi E. Hammond, Jon Iredell, Qiang Li, Sharon Micallef, Jennene Miller, Jayanthi Mysore, Colman Taylor, Paul J. Young, Brian H. Cuthbertson, Simon R. Finfer
Journal: JAMA (2022)

Importance Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain. Objective To determine whether SDD reduces in-hospital mortality in critically ill adults. Design, Setting, and Participants A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021. Interventions ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a 3-month interperiod gap. Patients in the SDD group (n = 2791) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191) received standard care. Main Outcomes and Measures The primary outcome was in-hospital mortality within 90 days. There were 8 secondary outcomes, including the proportion of patients with new positive blood cultures, antibiotic-resistant organisms (AROs), and Clostridioides difficile infections. For the ecological assessment, a noninferiority margin of 2% was prespecified for 3 outcomes including new cultures of AROs. Results Of 5982 patients (mean age, 58.3 years; 36.8% women) enrolled from 19 ICUs, all patients completed the trial. There were 753/2791 (27.0%) and 928/3191 (29.1%) in-hospital deaths in the SDD and standard care groups, respectively (mean difference, −1.7% [95% CI, −4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82-1.02]; P = .12). Of 8 prespecified secondary outcomes, 6 showed no significant differences. In the SDD vs standard care groups, 23.1% vs 34.6% had new ARO cultures (absolute difference, −11.0%; 95% CI, −14.7% to −7.3%), 5.6% vs 8.1% had new positive blood cultures (absolute difference, −1.95%; 95% CI, −3.5% to −0.4%), and 0.5% vs 0.9% had new C difficile infections (absolute difference, −0.24%; 95% CI, −0.6% to 0.1%). In 8599 patients enrolled in the ecological assessment, use of SDD was not shown to be noninferior with regard to the change in the proportion of patients who developed new AROs (−3.3% vs −1.59%; mean difference, −1.71% [1-sided 97.5% CI, −∞ to 4.31%] and 0.88% vs 0.55%; mean difference, −0.32% [1-sided 97.5% CI, −∞ to 5.47%]) in the first and second periods, respectively. Conclusions and Relevance Among critically ill patients receiving mechanical ventilation, SDD, compared with standard care without SDD, did not significantly reduce in-hospital mortality. However, the confidence interval around the effect estimate includes a clinically important benefit. Trial Registration ClinicalTrials.gov Identifier: NCT02389036